Small molecules are important targets with the potential of clinical or commercial applications such as medical diagnostics, environmental monitoring, and forensic science. Thus, efforts to develop methods for portable, low-cost, point-of-care and quantitative detection of a broad range of small molecules are gaining momentum.
Synthetic cathinones (also known as bath salts) are designer drugs sharing a similar core structure with amphetamines and 3, 4-methylenedioxy-methamphetamine (MDMA). They are highly addictive central nervous system stimulants, and are associated with many negative health consequences, including even death. Although these drugs have emerged only recently, abuse of bath salts has become a threat to public health and safety due to their severe toxicity, increasingly broad availability, and difficulty of regulation. More importantly, there is currently no reliable presumptive test for any synthetic cathinone. Chemical spot tests used to detect conventional drugs such as cocaine, methamphetamine, and opioids show no cross-reactivity to synthetic cathinones.
Screening for small molecules such as synthetic cathinones requires cross-reactive assays that can broadly detect small molecules based on their shared molecular framework. Such assays are more efficient and cost-effective than the tandem use of multiple highly specific assays that detect a single analyte.
Antibody-based immunoassays have dominated the field of on-site small-molecule detection, and while numerous assays have been developed for a variety of individual targets, the development of cross-reactive immunoassays has proven difficult. This is in part because the process of antibody generation, which is entirely in vivo, provides no control over the cross-reactivity of the generated antibody.
Nucleic acid-based bioaffinity elements known as aptamers hold much promise in overcoming many of the shortcomings associated with immunoassays. Aptamers are isolated through a process known as systematic evolution of ligands by exponential enrichment (SELEX) to bind targets of interest with high affinity and specificity. Aptamers can be isolated for essentially any target, including metal ions, small molecules, proteins, or whole cells.
Unlike antibodies, aptamers can be isolated relatively quickly and chemically synthesized in an inexpensive manner with no batch-to-batch variation. Aptamers are chemically stable and have shelf-lives of a few years at room temperature. Moreover, aptamers can be engineered to have tunable target-binding affinities or various functionalities. These advantages make aptamers ideal for use in biosensors.
Because SELEX is an in vitro process, it should be possible to isolate a cross-reactive aptamer through precise control of the selection strategy and conditions. Ideally, such aptamer should bind to the core structure of a given class of targets while being insensitive to peripheral substituents, thereby capable of recognizing the whole target family. However, little work has been done to demonstrate the capability of SELEX to achieve such goal.
Therefore, there is a need for developing a novel SELEX strategy to isolate cross-reactive aptamers for structurally-similar compounds. There are also needs for methods and materials for rapid, sensitive, on-site, and naked-eye detection of small molecules such as synthetic cathinones.